Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Not Recruiting

Trial ID: NCT00588770


This randomized phase III trial studies chemotherapy to see how well it works with or without bevacizumab in treating patients with head and neck squamous cell carcinoma that has come back (recurrent) or that has spread to other parts of the body (metastatic). Drugs used in chemotherapy, such as docetaxel, cisplatin, carboplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also make tumor cells more sensitive to chemotherapy and stop the growth of head and neck cancer by blocking blood flow to the tumor. It is not yet known whether combination chemotherapy is more effective when given with or without bevacizumab in treating patients with head and neck squamous cell carcinoma.

Official Title

A Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer

Stanford Investigator(s)

Harlan Pinto
Harlan Pinto

Associate Professor of Medicine (Oncology) and of Otolaryngology - Head & Neck Surgery

A. Dimitrios Colevas, MD
A. Dimitrios Colevas, MD

Professor of Medicine (Oncology) and, by courtesy, of Otolaryngology - Head & Neck Surgery (OHNS) and of Radiation Oncology (Radiation Therapy)


Inclusion Criteria:

   - Patients must have histologically or cytologically confirmed squamous cell cancer of
   the head and neck (SCCHN), from any primary site, including unknown primary cancers of
   the head and neck; patient must not have nasopharyngeal carcinoma of histologic types
   World Health Organization (WHO) 2 or 3 or squamous cell carcinoma that originated in
   the skin

   - Patients must have SCCHN that is either (a) recurrent, judged incurable by surgery or
   radiation or (b) metastatic; NOTE: Patients who refuse radical resection for recurrent
   disease are eligible; NOTE: A second primary squamous cell carcinoma of the head and
   neck is allowed if eligibility is based on a recurrent or metastatic first primary
   squamous cell carcinoma of the head and neck

   - No prior chemotherapy or biologic/molecular targeted therapy for recurrent or
   metastatic SCCHN

      - Patients may have received one regimen of induction, concomitant
      chemoradiotherapy and/or adjuvant chemotherapy as part of initial potential
      curative therapy but must not have received prior chemotherapy for recurrent or
      metastatic disease

      - A minimum of 4 months is required between last dose of chemotherapy or
      chemoradiotherapy and study treatment; in addition patients must be
      progression-free for at least 4 months after completion of chemotherapy or
      chemoradiotherapy or radiation plus cetuximab given with a curative intent;
      (cetuximab therapy: 4 months is required between last dose of chemotherapy or
      chemoradiotherapy and study treatment if part of concurrent regimen, 8 weeks if
      part of adjuvant regimen post radiation)

      - Patients having progression after 2 cycles of induction chemotherapy are not
      eligible for the study

   - No prior bevacizumab is allowed

   - A maximum of one prior radiotherapy regimen, curative or palliative, to the head and
   neck is allowed; if the radiation is combined with chemotherapy and/or cetuximab, a
   minimum of 4 months must elapse between the end of radiotherapy and registration; if
   the radiation is given alone, a minimum of 8 weeks must elapse between the end of
   radiotherapy and registration; a minimum of 3 weeks must elapse between prior
   radiation to other areas and registration

   - Patients must not be receiving any other investigational agent while on the study

   - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

   - Patients must have recovered to grade 1 or better from any acute effects of prior
   surgery, chemotherapy, or radiation therapy, and should be > 4 weeks post surgery;
   chronic late xerostomia, speech and swallowing abnormalities resulting from prior
   radiation or surgery are permitted if nutritional status is stable

   - Patients must have measurable disease based on Response Evaluation Criteria in Solid
   Tumors (RECIST); baseline measurements and evaluations of all sites of disease must be
   obtained =< 4 weeks prior to randomization; disease in previously irradiated sites is
   considered measurable if there has been unequivocal disease progression or
   biopsy-proven residual carcinoma following radiation therapy; persistent disease after
   radiotherapy must be biopsy proven at least 8 weeks after completion of radiation
   therapy; (radiographic findings are acceptable providing that clear-cut measurements
   can be made)

   - Absolute neutrophil count (ANC) >= 1500/mm^3

   - Hemoglobin (Hgb) >= 8.0 g/dL

   - Platelet count >= 100,000/mm^3

   - Creatinine clearance of >= 60 ml/min; creatinine clearance may be measured or
   calculated; if calculating, creatinine clearance, use the Cockroft-Gault formula

   - Total bilirubin within normal limits (must be obtained =< 2 weeks prior to

   - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) must be within the
   range allowing for eligibility

      - Alkaline phosphatase normal AND AST or ALT =< 5 x upper limit of normal (ULN)

      - Alkaline phosphatase > 1 but =< 2.5 x ULN AND AST or ALT > 1 but =< 1.5 x ULN

      - Alkaline phosphatase > 2.5 but =< 5 x ULN AND AST or ALT normal

   - Alkaline phosphatase must be within the range allowing for eligibility

   - Urine dipstick must be =< 0-1+ within 2 weeks (14 days) of randomization; if urine
   dipstick result is > 1+, a calculation of urine protein creatinine (UPC) ratio is
   required; patients must have a UPC ratio < 1.0 to participate in the study; NOTE: UPC
   ratio of spot urine is an estimation of the 24 urine protein excretion - a UPC ratio
   of 1 is roughly equivalent to a 24-hour urine protein of 1 gm

   - No known brain metastases

   - Patients who meet the following criteria will be excluded:

      - Tumors that invade major vessels (e.g. the carotid) as shown unequivocally by
      imaging studies

      - Central (i.e. within 2 cm from the hilum) lung metastases that are cavitary as
      shown unequivocally by imaging studies

      - Any prior history of bleeding related to the current head and neck cancer

      - History of gross hemoptysis (bright red blood of 1/2 teaspoon or more per episode
      of coughing) =< 3 months prior to enrollment

   - No history of coagulopathy or hemorrhagic disorders

   - Patients should not have a history of thrombosis (e.g. pulmonary embolism or deep
   venous thrombosis) currently requiring therapeutic anticoagulation (prophylactic use
   of warfarin 1 mg per day is allowed) and international normalized ratio (INR) should
   be < 1.5 at registration

   - Patients must not be receiving chronic daily treatment with aspirin (> 325 mg/day) or
   non-steroidal anti-inflammatory agents (NSAID's) known to inhibit platelet function;
   the use of anti-platelet agents (e.g. dipyridamole [Persantine], ticlopidine [Ticlid],
   clopidogrel [Plavix]) is allowed only if patient is not receiving aspirin or NSAID's
   known to inhibit platelet function

   - No hypercalcemia related to head and neck cancer

   - Patients with a prior history of squamous cell or basal carcinoma of the skin or in
   situ cervical cancer must have been curatively treated; patients with a history of
   other prior malignancy must have been treated with curative intent and must have
   remained disease-free for 3 years post diagnosis

   - No current peripheral neuropathy >= grade 2 at time of randomization

   - Patients must not have any co-existing condition that would preclude full compliance
   with the study

   - No prior history of severe hypersensitivity reaction to docetaxel or other drugs
   formulated with polysorbate 80, if the physician's choice of chemotherapy regimen is

   - All patients must have blood pressure =< 150/90 =< 2 weeks prior to randomization;
   patients with history of hypertension must be well-controlled upon study entry (=<
   150/90) on a stable regimen of anti-hypertensive therapy

   - No major surgical procedure, open biopsy, or significant traumatic injury within 28
   days prior to study enrollment, or anticipation of need for major surgical procedure
   during the course of the study

   - No unstable angina or myocardial infarction within the previous 6 months; no
   symptomatic congestive heart failure, New York Heart Association (NYHA) grade II or
   greater; no history of aortic dissection or presence of aneurysm > 6 cm (or at high
   risk for rupture); no serious cardiac arrhythmia requiring medication (history of
   chronic atrial fibrillation or other atrial arrhythmia with controlled rate on
   medication is allowed); no clinically significant peripheral vascular disease
   manifested by intermittent claudication or need for vascular intervention; no history
   of aortic dissection; no history of any central nervous system (CNS) cerebrovascular
   ischemia or stroke within the last 6 months; no active serious infection

   - Patients should not have prior history of a serious human anti-human antibody (HAHA)
   reaction; patients with known hypersensitivity to Chinese hamster ovary cell products
   or other recombinant human antibodies are not eligible

   - Women must not be pregnant or breast feeding; pregnant women are excluded from this
   study; women of child-bearing potential and men must agree to total abstinence or to
   use adequate hormonal or barrier method of birth control prior to study entry and for
   the duration of study participation; should a woman become pregnant or suspect she is
   pregnant while in this study, she should inform her treating physician immediately;
   all females of childbearing potential must have a blood test or urine study within 2
   weeks prior to randomization to rule out pregnancy

   - Human immunodeficiency virus (HIV)-positive patients receiving combination
   anti-retroviral therapy are excluded from the study; appropriate studies will be
   undertaken in patients receiving combination anti-retroviral therapy when indicated

   - No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal
   abscess within 6 months prior to registration


biological: bevacizumab

drug: cisplatin

drug: docetaxel

drug: fluorouracil

drug: carboplatin

other: Laboratory Biomarker Analysis

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305

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